CTBP1

Chr 4AD

C-terminal binding protein 1

Also known as: BARS, HADDTS

NCBI Gene: 1487ENSG00000159692UniProt: Q13363OMIM: 602618

CTBP1 encodes a transcriptional corepressor with dehydrogenase activity that controls Golgi structure and brown adipose tissue differentiation. Mutations cause hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.98), reflecting its critical role in development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.281 OMIM phenotype
Clinical Summary— CTBP1
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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
116 unique Pathogenic / Likely Pathogenic· 131 VUS of 429 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.28LOEUF
pLI 0.984
Z-score 3.60
OE 0.06 (0.02–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.31Z-score
OE missense 0.45 (0.39–0.52)
126 obs / 282.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.06 (0.02–0.28)
0≤0.351.4
Missense OE0.45 (0.39–0.52)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 1 / 17.0Missense obs/exp: 126 / 282.5Syn Z: 0.02
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCTBP1-related hypotonia, ataxia, developmental delay, and tooth enamel defect syndromeLOFAD
DN
0.4389th %ile
GOF
0.5465th %ile
LOF
0.71top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.28
DN1 literature citation

Literature Evidence

DNDecreased complex I and IV activities in skeletal muscle of our patient suggests that BAX expression is altered by mutated CtBP1, with the c.991C>T p.(Arg331Trp) variant acting in a dominant-negative mechanism to disrupt mitochondrial function.PMID:28955726

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

429 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic112
Likely Pathogenic4
VUS131
Likely Benign153
Benign8
Conflicting5
112
Pathogenic
4
Likely Pathogenic
131
VUS
153
Likely Benign
8
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
111
0
112
Likely Pathogenic
0
0
4
0
4
VUS
7
100
21
3
131
Likely Benign
0
9
58
86
153
Benign
0
0
4
4
8
Conflicting
—5
Total711019893413

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CTBP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients